Apoptosis And Stem Cells In Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$22,852,198.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks: enhanced cell survival and stem cell-like behaviour. As we discovered, cell death is often blocked in cancer cells. Hence, we are attempting to develop drugs that flip the natural ‘cell death switch’. Stem cells are rare cells that generate entire tissues, as we showed for the breast. Certain cancers may be driven by ‘rogue’ stem cells. If so, eradication of these rare cells within the bulk tumour may require novel therapies.
Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to ....Taming the intruders: the domestication of Tigger transposable elements in mammals. It has become apparent that most of the DNA that makes us what we are is actually comprised of the remnants of invading parasitic DNA acquired over time. A continual battle exists between host which tries to silence or remove this DNA, and the parasite that tries to multiply and spread. We are currently investigating an intriguing aspect of this process that involves host genomes 'domesticating' parasitic DNA to provide novel functions, thereby facilitating the evolution of specific characteristics within species.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100011
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, ....Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, biochemical and chemical probes with a focus on minimizing phototoxicity. Expected outcomes include new fundamental knowledge on molecular signal transduction and cell heterogeneity; development of novel probes and methodologies and the development of new and existing interdisciplinary research collaborations. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561229
Funder
Australian Research Council
Funding Amount
$518,427.00
Summary
Establishment of a Multiphoton Microscope Imaging Platform for Live Cell and Tissue, and Optical Imaging. This proposal seeks to establish a multidisciplinary multiphoton imaging laboratory, expanding the imaging capabilities of a Core Regional Imaging Facility. This Facility supports researchers across all Monash campuses and hospital-based research Schools, as well as outside research groups in the Victorian region. Furthermore, this equipment will support significant fiber optic research at V ....Establishment of a Multiphoton Microscope Imaging Platform for Live Cell and Tissue, and Optical Imaging. This proposal seeks to establish a multidisciplinary multiphoton imaging laboratory, expanding the imaging capabilities of a Core Regional Imaging Facility. This Facility supports researchers across all Monash campuses and hospital-based research Schools, as well as outside research groups in the Victorian region. Furthermore, this equipment will support significant fiber optic research at Victoria University for the development of communication and endoscopic technology. The instrument design will allow multiple use of the lightsource and choice of specific imaging devices (microscopes) to ensure that applications in biocellular imaging, intravital microscopy and fiber optic design and imaging are individually optimised.Read moreRead less
Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This k ....Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This knowledge will reveal how IPO5 controls formation of sperm by revealing what other proteins it binds to and how this affects cell signaling and responses to the environment.
Benefits: This will provide information about potential interventions to control fertility or to repair abnormal cells.
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Modelling human brain development with stem cells and biomaterials. With limited resources to directly study and advance our understanding of human neural development, this
proposal will establish models of 4 key stages. Employing innovative, interdisciplinary approaches, biomaterials will be fabricated to provide structural and chemical support for human stem cells during: (i) neural induction, (ii) specification into neuronal progenitor subpopulations, (iii) neuronal maturation and integration ....Modelling human brain development with stem cells and biomaterials. With limited resources to directly study and advance our understanding of human neural development, this
proposal will establish models of 4 key stages. Employing innovative, interdisciplinary approaches, biomaterials will be fabricated to provide structural and chemical support for human stem cells during: (i) neural induction, (ii) specification into neuronal progenitor subpopulations, (iii) neuronal maturation and integration into complex neural networks as well as, (iv) the organisation of neurons into larger 3-dimensional brain structures, namely folding of the human cortex. Further, biomaterials developed here have commercialisation potential, targeted at standardizing the culturing of human stem cells to defined neural populations.
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Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less
Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform o ....Engineering a technology platform for organoids. Protein delivery technologies hold great potential to improve organoids (miniature organs used as in vitro models), allowing a deep understanding of development. However, current limitations must be overcome - particularly cost, precision, and efficacy. This project will engineer delivery materials to improve the efficacy of organoids, allowing control over the location and timing of protein delivery. Outcomes will include a technology platform of immediate use in the agriculture sector and for animal model alternatives. The benefit will be widespread, ensuring the growth and sustainability of our health and agriculture sector. The project will increase public understanding of protein delivery technologies, aiding in technology adoption.Read moreRead less